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The American Association of Anatomists (AAA) lost a loyal and active member on July 31st, 2006 when Dr. Mark Nathanson died from a sudden heart attack. Dr. Nathanson, an Associate Professor in the Departments of Cell Biology and Molecular Medicine and Pediatrics at the University of Medicine and Dentistry of New Jersey (UMDNJ)-New Jersey Medical School in Newark, was a developmental biologist and an active member of AAA since 1982.1

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Illustration 1. Dr. Mark A. Nathanson (photo courtesy Dr. Curt Civin).

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Dr. Nathanson was a Visiting Professor in the Department of Pediatric Oncology at Johns Hopkins University School of Medicine, collaborating with the laboratory of Dr. Curt Civin, when stricken by a sudden cardiovascular incident in the Bunting-Blaustein Cancer Research Building lobby. At a memorial service on August 3, 2006, Dr. Curt Civin remarked that “Monday, July 31st was a typical day for Mark: he attended a lab meeting, reporting his results on the sabbatical research project studying the effects of Runx1 gene expression in human embryonic stem cells.” Later that day, Dr. Civin stated, “they excitedly argued how best to analyze Mark's new data from his project.” Many others that worked with Mark fondly remember his passion and hunger to discuss experiments and scientific theories.

Dr. Nathanson was a very active AAA member. He was elected to the Board of the Morphogenesis Club (MC) in 1983 and served as the president-elect of the MC in 1985. Mark served on the Second Century Fund and the Educational Affairs Committees. He also served AAA on the Advisory Committee of Young Anatomists, chairing the Jan Langman Award committee. In 2005, he was appointed to the Public Affairs Committee. Mark also organized many symposia for the AAA meetings, including the Morphogenesis Club Symposium, Educational Issues in Teaching Anatomy, a Refresher Course on Osteogenesis, and Cell Signaling in Musculoskeletal Differentiation.

Dr. Nathanson was born on October 11, 1947 to Lillian and Hy Nathanson in Cleveland, Ohio. He spent his childhood in Beachwood, a suburb of Cleveland, and obtained a B.A. in Chemistry and Zoology followed by a M.S. in Developmental Biology and Electron Microscopy from Miami University in Oxford, Ohio with Dr. Allan L. Allenspach. In December 1972, Mark married Jayne Gould, a fellow graduate student at Temple University. As was the tradition in the 1970s, Mark obtained another Master's degree, and then a Ph.D. (1977) in Developmental Biology under Dr. Robert Hilfer's guidance. His Ph.D. thesis project was published in 1978 in Developmental Biology, one of the first papers to report the formation of cartilage by non-chondrogenic cell types. This work shows that Dr. Nathanson was fascinated by how the microenvironment or niche contributed to the phenotype and genotype of a cell, well before much was known about cell-matrix interactions and receptors or signal transduction. He continued to study the environment-cell interaction effect on phenotype with Dr. Elizabeth D. Hay at Harvard Medical School from 1977–1979. Drs. Nathanson and Hay published two papers in Developmental Biology in 1980 on how skeletal muscle, grown on bone matrix, changed into cartilage cells. As an Assistant Professor at UMDNJ-New Jersey Medical School, Dr. Nathanson continued to investigate the regulation of skeletal muscle or mesenchymal cell transition into a cartilage phenotype via the cells' interaction with various extracellular matrices. This work elucidated the underlying molecular mechanisms that facilitated the “genotype switch” and was published in Proceedings of the National Academy of Sciences and Journal of Cell Biology in the mid and late 1980s. “We postdocs had a profound admiration for Mark, especially his ability to defend his innovative hypotheses to Harvard's members of the National Academy of Sciences,” said Dr. Mary J.C. Hendrix, who was a postdoctoral fellow with Mark and is now the President and Scientific Director of the Children's Memorial Research Center at Northwestern University.

Dr. Nathanson's early papers have been cited by many investigators studying stem cell niches and tissue engineering as recently as 2005. This shows that his seminal observations from the late 1970s and early 1980s have continued to influence scientific endeavors that are now being used to rebuild bone or as tissue engineering therapy. Dr. Nathanson holds a patent with Drs. Reddi and Sampath on a “Method for in vitro use of cartilage-inductive substances.” This patent has been referenced by 56 other patents that are in the tissue engineering field, indicating that the investigators were indeed pioneers in understanding bone matrix therapy.

Requesting a sabbatical to study stem cell biology was a natural progression for Dr. Nathanson's interest in cell-matrix interactions and developmental differentiation. Dr. Curt Civin invited Mark to join his group at Johns Hopkins to tackle the very difficult task of “investigating human embryonic stem cells as a model of embryonic hematopoiesis and studying the effects of the Runx 1 gene in the system.” Dr. Civin added that “Mouse knockout models demonstrate that the Runx1 hematopoietic master regulatory gene is necessary for primitive embryonic hematopoiesis, but not for definitive hematopoiesis. If Runx1 is conditionally inactivated in adult mice, hematopoiesis gradually becomes progressively abnormal and ultimately generates leukemias. Dominant negative mutants involving Runx1 result in leukemias in humans, yet inhibition of Runx1 function by these dominant inhibitory oncogenes results in G1 arrest—a surprising effect for an oncogene.” Mark's sabbatical studies were designed to develop an in vitro model system for human embryonic stem cells to allow detailed cell and molecular mechanistic studies involved in normal and malignant development. The first studies were to investigate Runx1 in the model system, followed by the later use of the system as a general investigative tool. Eventually, Mark planned to take his expertise in human embryonic stem cell biology back “home” to his research on muscle and cartilage development.

Dr. Nathanson was appointed as an Assistant Professor at UMDNJ, New Jersey Medical School in 1979 and was promoted to Associate Professor in 1986. His research was supported by several NIH grants, including a Research Career Development Award and two other NIH grants. In addition, he obtained funding from the UMDNJ Foundation and the Musculoskeletal Transplant Foundation. Dr. Nathanson also served on many NIH study sections and reviewed grants for the National Science Foundation, the Swiss National Science Foundation, The March of Dimes, and the Israel Binational Science Fund.

Dr. Nathanson enthusiastically lectured in human anatomy, microanatomy, embryology and cell biology courses. He developed a cell and tissue biology course for graduate and summer students. Over a period of 13 years, he was the course administrator, working closely with Dr. Amos Gona, the course director of Cell and Tissue Biology (CTB) for medical students. Dr. Gona remarked that “he painstakingly developed an extensive question bank and put together all the unit exams for the course. Mark also developed a website for CTB and was the first to use PowerPoint presentations for lectures. His technological expertise and willingness to help colleagues were instrumental in upgrading the CTB course. His contribution was well recognized and appreciated, and it was anticipated that Mark would have had a leading role in switching the histology laboratories to a virtual format next spring.” In addition to teaching at UMDNJ, Dr. Nathanson also taught Embryology in the Biology Department at Temple University for several years after Dr. Hilfer retired.

Dr. Nathanson ardently mentored several graduate and medical students throughout his career. Mark also mentored Charles Vanderburg, a Ph.D. candidate, and they identified a small non-polyadenylated RNA moiety that temporally regulated the translation of a subset of skeletal muscle proteins during development in a neonatal rat model. This early description of what would come to be known as an miRNA was published in the Journal of Cell Biology in 1987, once again providing testament to Mark's propensity for innovative thought and hypotheses that were ahead of their time. Dr. Vanderburg is currently the Director of Advanced Tissue Resource Center which is part of the Harvard Center for Neurodegeneration and Repair and the Mass General Institute for Neurodegenerative Disease.

In addition to his service to AAA, Dr. Nathanson was also a member of the American Society for Cell Biology (ASCB) and the Orthopedic Research Society. He co-chaired sessions as a graduate student and postdoctoral fellow for ASCB. For many years, Mark used his gifted photography skills to document the ASCB meeting events and members. Many people will remember him as the guy behind the camera at ASCB meetings.

Dr. Nathanson is survived by his loving wife, Jayne Nathanson, his mother Lillian, and sisters Susan and Elyse. Mark also leaves behind many colleagues who miss him dearly, including the faculty and staff at the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, UMDNJ Newark, and former members of Elizabeth D. Hay's laboratory at Harvard Medical School. Needless to say, his AAA colleagues will also miss Mark's wit and smile at the Experimental Biology meetings.